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Lineage analysis of intestinal stem cells and development of the culture system to study the stem cell niche

Research Project

Project/Area Number 15K07136
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Morphology/Structure
Research InstitutionNippon Medical School

Principal Investigator

ISHIZUYA-OKA Atsuko  日本医科大学, 医学部, 教授 (50175254)

Co-Investigator(Renkei-kenkyūsha) HASEBE Takashi  日本医科大学, 医学部, 准教授 (70329027)
FUJIMOTO Kenta  日本医科大学, 医学部, 講師 (50403580)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords小腸 / 幹細胞 / Ror2 / Wntシグナル経路 / 甲状腺ホルモン / 変態 / 培養 / アフリカツメガエル / Wntシグナル伝達経路
Outline of Final Research Achievements

In the Xenopus laevis intestine during metamorphosis, thyroid hormone (TH) induces some epithelial cells that express Ror2 to dedifferentiate into stem cells. In the present study, to clarify molecular mechanisms underlying the formation of stem cell niche, we histocytochemically identified precursors of the stem cells using transgenic frogs and developed a culture system for them. In addition, we performed in vitro analyses of TH response genes and found that both canonical Wnt and Notch signaling pathways are activated in the stem cells from their appearance and promote their proliferation. Furthermore, we have shown that hyaluronan newly synthesized by TH activates the Wnt pathway via CD44, suggesting the important role of hyaluronan in the formation of stem cell niche.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (18 results)

All 2018 2017 2016 2015 Other

All Journal Article (8 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 7 results,  Open Access: 2 results,  Acknowledgement Compliant: 4 results) Presentation (9 results) (of which Invited: 1 results) Remarks (1 results)

  • [Journal Article] Essential roles of thyroid hormone-regulated hyaluronan/CD44 signaling in adult stem cell development during Xenopus laevis intestinal remodeling2017

    • Author(s)
      Hasebe T, Fujimoto K, Kajita M, Ishizuya-Oka A
    • Journal Title

      Stem Cells

      Volume: 35 Issue: 10 Pages: 2175-2183

    • DOI

      10.1002/stem.2671

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Organ Culture of the Xenopus Tadpole Intestine2017

    • Author(s)
      Ishizuya-Oka Atsuko
    • Journal Title

      Cold Spring Harbor Protocols

      Volume: 2017 Issue: 10 Pages: pdb.prot097683-pdb.prot097683

    • DOI

      10.1101/pdb.prot097683

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Functional analysis of thyroid hormone receptor beta in Xenopus tropicalis founders using CRISPR-Cas2017

    • Author(s)
      Sakane Y, Iida M, Hasebe T, Fujii S, Buchholz DR, Ishizuya-Oka A, Yamamoto T, Suzuki KT
    • Journal Title

      Biology Open

      Volume: 7 Pages: 1-9

    • DOI

      10.1242/bio.030338

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Thyroid hormone-induced activation of Notch signaling is required for adult intestinal stem cell development during Xenopus laevis metamorphosis2017

    • Author(s)
      Hasebe T, Fujimoto K, Kajita M, Fu L, Shi Y-B, Ishizuya-Oka A
    • Journal Title

      Stem Cells

      Volume: 35 Issue: 4 Pages: 1028-1039

    • DOI

      10.1002/stem.2544

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] How thyroid hormone regulates transformation of larval epithelial cells into adult stem cells in the amphibian intestine.2017

    • Author(s)
      Ishizuya-Oka, A
    • Journal Title

      Molecular and Cellular Endocrinology

      Volume: 印刷中 Pages: 98-103

    • DOI

      10.1016/j.mce.2017.02.026

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Growth, development, and intestinal remodeling occurs in the absence of thyroid hormone receptor alpha in tadpoles of Xenopus tropicalis.2017

    • Author(s)
      Choi, J.A., Ishizuya-Oka, A., Buchholz D.R.
    • Journal Title

      Endocrinology

      Volume: 印刷中 Issue: 6 Pages: 1623-1633

    • DOI

      10.1210/en.2016-1955

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Thyroid hormone activates Wnt/beta-catenin signaling involved in adult epithelial development during Xenopus laevis intestinal remodeling2016

    • Author(s)
      Hasebe, T., Fujimoto K., Kajita M., Ishizuya-Oka, A.
    • Journal Title

      Cell & Tissue Research

      Volume: 印刷中

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] 消化器系の進化と発生のメカニズム2015

    • Author(s)
      岡 敦子
    • Journal Title

      日本医科大学医学会雑誌

      Volume: 11 Pages: 155-160

    • NAID

      130005087592

    • Related Report
      2015 Research-status Report
  • [Presentation] アフリカツメガエル小腸におけるヒアルロン酸シグナルの幹細胞ニッチ形成に果たす役割2018

    • Author(s)
      藤本健太、長谷部孝、梶田満子、岡敦子
    • Organizer
      第123回日本解剖学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] アフリカツメガエルの小腸再構築におけるヒアルロン酸シグナルの役割2017

    • Author(s)
      藤本健太、長谷部孝、梶田満子、岡敦子
    • Organizer
      第50回日本発生生物会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] アフリカツメガエル消化管再構築の分子基盤:Notch シグナルの役割2017

    • Author(s)
      長谷部孝、岡敦子
    • Organizer
      第88回日本動物学会シンポジウム「両生類はワンダーランド」
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] アフリカツメガエル小腸上皮の幹細胞制御におけるヒアルロン酸/CD44シグナルの役割2017

    • Author(s)
      長谷部孝、藤本健太、梶田満子、岡敦子
    • Organizer
      第88回日本動物学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 無尾両生類の変態における幽門形成の組織学と遺伝子発現2017

    • Author(s)
      名倉京、佐藤夢子、長谷部孝、岡敦子、平良眞規
    • Organizer
      第40回日本分子生物会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] アフリカツメガエルの消化管再構築におけるヒアルロン酸合成酵素の遺伝子発現解析2016

    • Author(s)
      藤本 健太、長谷部 孝、梶田 満子、岡 敦子
    • Organizer
      第39回日本分子生物会大会
    • Place of Presentation
      パシフィコ横浜(神奈川・横浜)
    • Year and Date
      2016-12-02
    • Related Report
      2016 Research-status Report
  • [Presentation] Thyroid hormone-induced activation of Notch signaling is required for intestinal remodeling during Xenopus laevis metamorphosis2016

    • Author(s)
      長谷部 孝、藤本 健太、梶田 満子、Fu L.、Shi Y.-B.、岡 敦子
    • Organizer
      第87回日本動物学会大会
    • Place of Presentation
      沖縄コンベンションセンター(沖縄・宜野湾)
    • Year and Date
      2016-11-17
    • Related Report
      2016 Research-status Report
  • [Presentation] アフリカツメガエルの消化管再構築においてWntシグナルは甲状腺ホルモンにより活性化され成体型上皮の発生に関与する2016

    • Author(s)
      長谷部 孝、藤本 健太、岡 敦子
    • Organizer
      第57回日本組織細胞化学会学術集会
    • Place of Presentation
      杏林大学井の頭キャンパス(東京・三鷹)
    • Year and Date
      2016-09-03
    • Related Report
      2016 Research-status Report
  • [Presentation] ツメガエル変態期の消化管再構築におけるNotchシグナルの役割:DLL1とDLL2の発現解析2015

    • Author(s)
      長谷部孝、梶田満子、岡敦子
    • Organizer
      第86回日本動物学会大会
    • Place of Presentation
      朱鷺メッセ:新潟コンベンションセンター(新潟)
    • Year and Date
      2015-09-19
    • Related Report
      2015 Research-status Report
  • [Remarks] 日本医科大学知的財産推進センター

    • URL

      http://tlo.nms.ac.jp/researcher/762.html

    • Related Report
      2017 Annual Research Report 2016 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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